A Novel Platelet Activating Factor Antagonist, SM-12502, Attenuates Endotoxin-induced Disseminated Intravascular Coagulation and Acute Pulmonary Vascular Injury by Inhibiting TNF Production in Rats

Kazunori Murakami; Kenji Okajima; Mitsuhiro Uchiba; Masayoshi Johno; Hiroaki Okabe; Kiyoshi Takatsuki

doi:10.1055/s-0038-1650402

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1996; 75(06): 965-970
DOI: 10.1055/s-0038-1650402

Original Article

Schattauer GmbH Stuttgart

A Novel Platelet Activating Factor Antagonist, SM-12502, Attenuates Endotoxin-induced Disseminated Intravascular Coagulation and Acute Pulmonary Vascular Injury by Inhibiting TNF Production in Rats

Kazunori Murakami

¹The Department of Medicine, Kumamoto University Medical School, Kumamoto, Japan

,

Kenji Okajima

²The Department of Laboratory Medicine and Kumamoto University Medical School, Kumamoto, Japan

,

Mitsuhiro Uchiba

¹The Department of Medicine, Kumamoto University Medical School, Kumamoto, Japan

,

Masayoshi Johno

³The Department of Dermatology, Kumamoto University Medical School, Kumamoto, Japan

,

Hiroaki Okabe

²The Department of Laboratory Medicine and Kumamoto University Medical School, Kumamoto, Japan

,

Kiyoshi Takatsuki

¹The Department of Medicine, Kumamoto University Medical School, Kumamoto, Japan

› Author Affiliations

Abstract

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Summary

Adult respiratory distress syndrome and disseminated intravascular coagulation are important pathologic conditions affecting the outcome of patients with sepsis. To elucidate the possible therapeutic efficacy of SM-12502, a novel platelet activating factor antagonist, on acute lung injury and disseminated intravascular coagulation in sepsis, we investigated the effect of SM-12502 on an endotoxin (ET)-induced septic model in rats. SM-12502 prevented ET-induced increases in pulmonary vascular permeability and ET-induced histologic changes, such as leukocyte infiltration and pulmonary interstitial edema, 6 h following the administration of ET (5 mg/kg). SM-12502 also inhibited the decrease in fibrinogen and the increase in fibrin and fibrinogen degradation products observed following ET administration. SM-12502 prevented increases in the serum concentration of tumor necrosis factor (TNF) 90 min following ET administration in vivo, and significantly inhibited the production of TNF-α by ET-stimulated monocytes in vitro.

These findings suggest that SM-12502 attenuates the actions of endotoxin by the inhibition of TNF production

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References

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